1. Field of the Invention
The present invention relates to a biologically active substance-immobilized carrier comprising phosphazene polymer, a carrier comprising phosphazene polymer for immobilizing a biologically active substance, process as for a production thereof, and to the use thereof.
2. Description of the Related Art
Although biologically active substances such as antibodies, enzymes and the like are usually present in a form of solution, if they are immobilized on a solid carrier, their usefulness is largely expanded. The nature of the solid carrier, however, has various limitations, depending on the use of the carrier. For example, where the solid carrier is used for an affinity chromatography, the solid carrier must not adsorb substances other than a desired substance, i.e., a non-specific adsorption will not occur. Accordingly, to use of a synthetic polymer as a carrier for an affinity chromatography is not always successful, and currently, modified carbohydrate materials derived from naturally occurring carbohydrates such as agarose, cellulose and the like are mainly used.
Nevertheless, since synthetic polymer carriers are advantageous in comparison with modified carbohydrate carriers, in that they can be easily shaped, are resistant to on infection of microorganisms such as fungi, to a high pressure, and a high flow rate, many attempts have been made to use carbohydrate materials as an affinity chromatography carrier and some are actually used. It should be noted, however, that synthetic polymer carriers are disadvantageous in that an activity of a biologically active substance immobilized on a synthetic polymer carrier is lower than that of a biologically active substance immobilized on a carbohydrate carrier.
Japanese Unexamined Patent Publication (Kokai) No. 1-30650 describes a carrier comprising phosphazene polymer for immobilizing a biologically active substance wherein functional groups capable of immobilizing a biologically active substance (ligand) (or groups which can be converted to functional groups capable of immobilizing a biologically active substance) have been introduced in a surface lower portion of the carrier. The functional groups are introduced by treating a shaped polyphosphazene article.
Macromolecules 19 (6) 1505, (1986) describes an immobilization of an enzyme using a carrier wherein polybisaryloxyphosphazene is carried in porous alumina and amino groups are introduced in the phosphazene polymer present in a surface lower portion of the carrier.
When using the above-mentioned carriers in affinity chromatography or diagnostics, however, if side chains not having a functional group capable of bringing a ligand are hydrophobic, substances other than those having an affinity to the ligand are adsorbed to the carrier via the hydrophobic side chains, resulting in a lowering of the separation efficiency and diagnostic accuracy.
In the carrier described in the Japanese Unexamined Patent Publication (Kokai) No. 1-30650, since many functional groups capable of binding a biologically active substance exist, a large amount of the biologically active substance can be quantitatively immobilized, but sometimes a third dimensional structure of a biologically active substance is changed and an active site of the biologically active substance is inactivated by the functional groups. Moreover, functional groups which are not bonded to the biologically active substance could bind to biologically active substances other than that which should be a ligand, and if such solid carriers are used in affinity chromatography, a desired substance may be contaminated with substances not having an affinity to the ligand.